Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells
This study shows that the non-steroidal anti-inflammatory drug (NSAID) celecoxib and its non-cyclooxygenase-2 (COX2) analogue dimethylcelecoxib (DMC) exert a potent inhibitory effect on the growth of human cervix HeLa multi-cellular tumor spheroids (MCTS) when added either at the beginning (“prevent...
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MDPI AG
2020-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/12/463 |
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| author | Diana Xochiquetzal Robledo-Cadena Juan Carlos Gallardo-Pérez Víctor Dávila-Borja Silvia Cecilia Pacheco-Velázquez Javier Alejandro Belmont-Díaz Stephen John Ralph Betsy Alejandra Blanco-Carpintero Rafael Moreno-Sánchez Sara Rodríguez-Enríquez |
| author_facet | Diana Xochiquetzal Robledo-Cadena Juan Carlos Gallardo-Pérez Víctor Dávila-Borja Silvia Cecilia Pacheco-Velázquez Javier Alejandro Belmont-Díaz Stephen John Ralph Betsy Alejandra Blanco-Carpintero Rafael Moreno-Sánchez Sara Rodríguez-Enríquez |
| author_sort | Diana Xochiquetzal Robledo-Cadena |
| collection | DOAJ |
| description | This study shows that the non-steroidal anti-inflammatory drug (NSAID) celecoxib and its non-cyclooxygenase-2 (COX2) analogue dimethylcelecoxib (DMC) exert a potent inhibitory effect on the growth of human cervix HeLa multi-cellular tumor spheroids (MCTS) when added either at the beginning (“preventive protocol”; IC<sub>50</sub> = 1 ± 0.3 nM for celecoxib and 10 ± 2 nM for DMC) or after spheroid formation (“curative protocol”; IC<sub>50</sub> = 7.5 ± 2 µM for celecoxib and 32 ± 10 µM for DMC). These NSAID IC<sub>50</sub> values were significantly lower than those attained in bidimensional HeLa cells (IC<sub>50</sub> = 55 ± 9 µM celecoxib and 48 ± 2 µM DMC) and bidimensional non-cancer cell cultures (3T3 fibroblasts and MCF-10A mammary gland cells with IC<sub>50</sub> from 69 to >100 µM, after 24 h). The copper-based drug casiopeina II-gly showed similar potency against HeLa MCTS. Synergism analysis showed that celecoxib, DMC, and casiopeinaII-gly at sub-IC<sub>50</sub> doses increased the potency of cisplatin, paclitaxel, and doxorubicin to hinder HeLa cell proliferation through a significant abolishment of oxidative phosphorylation in bidimensional cultures, with no apparent effect on non-cancer cells (therapeutic index >3.6). Similar results were attained with bidimensional human cervix cancer SiHa and human glioblastoma U373 cell cultures. In HeLa MCTS, celecoxib, DMC and casiopeina II-gly increased cisplatin toxicity by 41–85%. These observations indicated that celecoxib and DMC used as adjuvant therapy in combination with canonical anti-cancer drugs may provide more effective alternatives for cancer treatment. |
| first_indexed | 2024-03-10T14:03:37Z |
| format | Article |
| id | doaj.art-134dac971f804a488c2cc2d6398ae07c |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T14:03:37Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-134dac971f804a488c2cc2d6398ae07c2023-11-21T00:48:53ZengMDPI AGPharmaceuticals1424-82472020-12-01131246310.3390/ph13120463Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer CellsDiana Xochiquetzal Robledo-Cadena0Juan Carlos Gallardo-Pérez1Víctor Dávila-Borja2Silvia Cecilia Pacheco-Velázquez3Javier Alejandro Belmont-Díaz4Stephen John Ralph5Betsy Alejandra Blanco-Carpintero6Rafael Moreno-Sánchez7Sara Rodríguez-Enríquez8Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico City 14080, MexicoDepartamento de Bioquímica, Instituto Nacional de Cardiología, Mexico City 14080, MexicoLaboratorio de Oncología Experimental, Instituto Nacional de Pediatría, Mexico City 14080, MexicoDepartamento de Bioquímica, Instituto Nacional de Cardiología, Mexico City 14080, MexicoDepartamento de Bioquímica, Instituto Nacional de Cardiología, Mexico City 14080, MexicoMenzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, QLD 4222, AustraliaDepartamento de Bioquímica, Instituto Nacional de Cardiología, Mexico City 14080, MexicoDepartamento de Bioquímica, Instituto Nacional de Cardiología, Mexico City 14080, MexicoDepartamento de Bioquímica, Instituto Nacional de Cardiología, Mexico City 14080, MexicoThis study shows that the non-steroidal anti-inflammatory drug (NSAID) celecoxib and its non-cyclooxygenase-2 (COX2) analogue dimethylcelecoxib (DMC) exert a potent inhibitory effect on the growth of human cervix HeLa multi-cellular tumor spheroids (MCTS) when added either at the beginning (“preventive protocol”; IC<sub>50</sub> = 1 ± 0.3 nM for celecoxib and 10 ± 2 nM for DMC) or after spheroid formation (“curative protocol”; IC<sub>50</sub> = 7.5 ± 2 µM for celecoxib and 32 ± 10 µM for DMC). These NSAID IC<sub>50</sub> values were significantly lower than those attained in bidimensional HeLa cells (IC<sub>50</sub> = 55 ± 9 µM celecoxib and 48 ± 2 µM DMC) and bidimensional non-cancer cell cultures (3T3 fibroblasts and MCF-10A mammary gland cells with IC<sub>50</sub> from 69 to >100 µM, after 24 h). The copper-based drug casiopeina II-gly showed similar potency against HeLa MCTS. Synergism analysis showed that celecoxib, DMC, and casiopeinaII-gly at sub-IC<sub>50</sub> doses increased the potency of cisplatin, paclitaxel, and doxorubicin to hinder HeLa cell proliferation through a significant abolishment of oxidative phosphorylation in bidimensional cultures, with no apparent effect on non-cancer cells (therapeutic index >3.6). Similar results were attained with bidimensional human cervix cancer SiHa and human glioblastoma U373 cell cultures. In HeLa MCTS, celecoxib, DMC and casiopeina II-gly increased cisplatin toxicity by 41–85%. These observations indicated that celecoxib and DMC used as adjuvant therapy in combination with canonical anti-cancer drugs may provide more effective alternatives for cancer treatment.https://www.mdpi.com/1424-8247/13/12/463Bliss-type additivism modelcelecoxibdimethylcelecoxibdrug synergismHeLa cellsresistance index |
| spellingShingle | Diana Xochiquetzal Robledo-Cadena Juan Carlos Gallardo-Pérez Víctor Dávila-Borja Silvia Cecilia Pacheco-Velázquez Javier Alejandro Belmont-Díaz Stephen John Ralph Betsy Alejandra Blanco-Carpintero Rafael Moreno-Sánchez Sara Rodríguez-Enríquez Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells Pharmaceuticals Bliss-type additivism model celecoxib dimethylcelecoxib drug synergism HeLa cells resistance index |
| title | Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells |
| title_full | Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells |
| title_fullStr | Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells |
| title_full_unstemmed | Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells |
| title_short | Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells |
| title_sort | non steroidal anti inflammatory drugs increase cisplatin paclitaxel and doxorubicin efficacy against human cervix cancer cells |
| topic | Bliss-type additivism model celecoxib dimethylcelecoxib drug synergism HeLa cells resistance index |
| url | https://www.mdpi.com/1424-8247/13/12/463 |
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